Pharmacological interactions between delta 1-trans-tetrahydrocannabinol (THC), the primary active constituent of cannabis, and other cannabinoids, also commonly found in cannabis, will be examined in the rat. It is possible that cannabinoids such as cannabidiol (CBD), cannabinol (CBN), whose chemical structures are similar to that of THC, may influence the pharmacological activity of cannabis by altering the biological disposition of THC. Similarly, THC may influence the disposition of the other cannabinoids. THC/cannabinoid dose-response relationships will be studied using measures of rotarod performance, locomotor activity and body temperature as indices of drug effect. The biliary excretion and tissue distribution of THC, CBD and CBN will be studied individually and in cannabinoid combinations, at doses of significant behavioral or physiological interaction. THC and its primary metabolite, 7-hydroxy-THC are normally bound up to 99% by lipoprotein and albumin in blood. Studies of the effects of phenylbutazone and dicumarol, which are transported in the blood in a protein-bound form, on the plasma protein binding and disposition of THC and its metabolites will be carried out. Blood plasma samples obtained from rats treated with 14C-THC and an interacting drug will be subjected to ultracentrifugation to permit a determination of the protein binding pattern of THC and its metabolites. Drugs causing an alteration of the plasma protein binding of THC and its metabolites, and hence tissue availability, could influence the pharmacological activity of THC.